Many types of cancers are associated with new blood vessel formation, a process known as angiogenesis. Several mechanisms involved in tumor-induced angiogenesis have been elucidated. The most direct of these mechanisms is the secretion by the tumor cells of cytokines with angiogenic properties, including tumor necrosis factor α (TNF-α).
A variety of other diseases and disorders are also associated with or characterized by undesired angiogenesis. For example, enhanced or unregulated angiogenesis has been implicated in a number of diseases and medical conditions, including, but not limited to, ocular neovascular diseases, choroidal neovascular diseases, retina neovascular diseases, rubeosis (neovascularization of the angle), viral diseases, genetic diseases, inflammatory diseases, allergic diseases, and autoimmune diseases. Examples of such diseases and conditions include, but are not limited to, diabetic retinopathy, retinopathy of prematurity, corneal graft rejection, neovascular glaucoma, retrolental fibroplasia, arthritis, and proliferative vitreoretinopathy.
Certain isoindole-1,3-dione compounds, e.g., 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione, have been reported to be capable of controlling angiogenesis or inhibiting the production of TNF-α, and useful in the treatment and prevention of various diseases and conditions. See U.S. Pat. No. 5,635,517, the disclosure of which is incorporated herein by reference in its entirety.
Processes for preparing certain isoindoline-1,3-dione compounds have been described, for example, in U.S. Pat. Nos. 5,635,517; 6,395,754; and 7,994,327; the disclosure of each of which is incorporated herein by reference in its entirety. A need still exists for efficient processes for preparing isoindoline-1,3-dione compounds.